Breaking News
August 20, 2018 - New assay may help improve both sarcoma diagnosis and treatment
August 20, 2018 - New class of insect repellents to fight against mosquito-borne diseases
August 20, 2018 - ACA Coverage Gains Include Workers Without Insurance
August 20, 2018 - 3-D printed biomaterials for bone tissue engineering
August 20, 2018 - Prenatal exposure to acute stress can affect cognitive function in children of low-income households
August 20, 2018 - Researchers find long-term structural, functional brain abnormalities in individuals with AUDs
August 20, 2018 - Shortage of insurance fraud cops sparks campaign debate
August 20, 2018 - Researchers find STAT3 as therapeutic target for chronic active EBV infection
August 20, 2018 - Health Tip: Keep Diabetic Feet Healthier
August 20, 2018 - FDA approves brain stimulation device for OCD
August 20, 2018 - NYU Langone’s Perlmutter Cancer Center expands Blood and Marrow Transplant Program
August 20, 2018 - New drug shows potential to prevent painful side effect of therapy
August 20, 2018 - RDMD raises $3 million in seed funding to accelerate rare disease research, drug development
August 20, 2018 - Illicit drug use is higher during celebratory events, may be worse than previously thought
August 20, 2018 - Exploring the relationship between fever and cancer incidence
August 20, 2018 - Study reveals how socioeconomic status affects racial, ethnic disparities in childhood cancer survival
August 20, 2018 - Brain tumors trap immune cells needed to fight cancer in the bone marrow, finds research
August 20, 2018 - Three factors that contribute to physician burnout
August 20, 2018 - Babies dependent on opioids need touch, not tech
August 20, 2018 - Understanding How Antibodies Shape the Gut Microbiome
August 20, 2018 - Cara Therapeutics Doses First Patient in Second Pivotal Phase 3 Efficacy Trial of Korsuva (CR845/difelikefalin) Injection in Hemodialysis Patients with Chronic Kidney Disease-Associated Pruritus
August 20, 2018 - Kidney transplant chains more effective in saving lives
August 20, 2018 - Study unravels cellular and molecular mechanisms behind dermal condensate formation
August 20, 2018 - New integrated gene logic-chips could have great value in medical care
August 20, 2018 - FDA Advisory Committee Recommends Approval of Paratek’s Omadacycline
August 20, 2018 - Total, open repairs decline for abdominal aortic aneurysms
August 20, 2018 - Novel system can pinpoint ingestible implants inside the body using wireless signals
August 20, 2018 - Infection rates of high risk oral HPV in England found to be lower than expected
August 20, 2018 - Making robots as valuable and trustworthy assistants for medical therapies
August 20, 2018 - Patients with low-risk blood clots can be better treated at home than at hospital
August 20, 2018 - Passive smoking exposure among kids greatly increases COPD risk late in life
August 20, 2018 - Primary Care Provider Burnout Rate Low in Small Practices
August 20, 2018 - Discovery presents treatment hope for Alzheimer’s and other neurodegenerative diseases
August 20, 2018 - Stroke patients appear to receive better care at teaching hospitals with less chance of readmission
August 20, 2018 - Distinct origin of ADHD identified In children with history of traumatic brain injury
August 20, 2018 - AHA: Wildfire Smoke Threatens Health of Those Near and Far
August 20, 2018 - Here’s a mental health workout that’s as simple as ABC
August 20, 2018 - Newly discovered cytoskeleton utilized by cancer cells for survival
August 19, 2018 - Bifidobacteria supplement colonizes gut of breastfed infants
August 19, 2018 - Why patients with Alzheimer’s markers never develop the condition
August 19, 2018 - ACA’s Medicaid expansion associated with increase in prescriptions for opioid use disorder treatment
August 19, 2018 - Important factor may be missing in models used to predict spread of epidemics from climate change
August 19, 2018 - Indian-Americans have fewer sudden infant deaths, study finds
August 19, 2018 - Experts advise against universal genomic screening of newborns
August 19, 2018 - New trial to investigate whether weight loss before conception can make mom and baby healthier
August 19, 2018 - Sun Pharma Announces FDA Approval of Cequa (cyclosporine) Ophthalmic Solution to Treat Dry Eye Disease
August 19, 2018 - Researchers examining Parkinson’s resilience
August 19, 2018 - HPI, INTEGRIS and USPI enter into agreement to offer patients more choice, flexibility of care
August 19, 2018 - Researchers find mechanism that prepares brain to replicate repeated actions
August 19, 2018 - Those who are emotionally stable when young may remain the most stable as they age
August 19, 2018 - URI professor develops simpler and quicker method for detecting impurity in heparin
August 19, 2018 - Mayo Medical Laboratories and NDSC collaborate to develop new patient blood-management solution
August 19, 2018 - Insight into endocrine cancers and treatment options
August 19, 2018 - HPV Legislation Doesn’t Impact Teen Sexual Behaviors
August 19, 2018 - Exenatide treatment alleviated symptoms of depression in patients
August 19, 2018 - Tufts researchers win grant to study integration of genomic sequencing into neonatal care
August 19, 2018 - Novel finger-prick test can help prevent toxoplasmosis
August 19, 2018 - Cosmetic Procedures Boost Well-Being, Poll Shows
August 19, 2018 - Responsive parenting intervention results in lower BMIs through age three
August 19, 2018 - Anticancer drugs can help plants to battle infection
August 19, 2018 - Sunscreen from bathers releases significant quantities of polluting titanium dioxide into the sea
August 19, 2018 - Case Western Reserve gets three-year grant to enhance food systems in Cleveland neighborhoods
August 19, 2018 - Teenagers can thank their parents’ positive attitude for avoiding obesity
August 19, 2018 - Body mass index positively linked with blood pressure
August 19, 2018 - New tool fills gap in Small Molecules market
August 19, 2018 - Study compares survival outcomes in rural and urban cancer patients enrolled in clinical trials
August 19, 2018 - Researchers develop molecular matrix that delivers healing stem cells to injured elderly muscles
August 19, 2018 - Teva and Regeneron Announce Positive Topline Phase 3 Fasinumab Results in Patients with Chronic Pain from Osteoarthritis of the Knee or Hip
August 19, 2018 - New study pinpoints ways to improve quality of food and nutrition research
August 19, 2018 - Ology Bioservices wins $8.4 million worth agreement to manufacture anti-Ebola monoclonal antibody
August 19, 2018 - New CRISPR technology may help eliminate mutated gene sequence
August 19, 2018 - “Zombie gene” protects elephants from cancer finds study
August 19, 2018 - Study explores how many American cities protect the rights of employed breastfeeding mothers
August 19, 2018 - FDA Approves Lenvima (lenvatinib) for First-line Treatment of Unresectable Hepatocellular Carcinoma (HCC)
August 19, 2018 - Pain: Considering Complementary Approaches (eBook)
August 19, 2018 - Autoimmune response drives vision loss in glaucoma
August 19, 2018 - Tandem Diabetes Care introduces t:slim X2 Insulin Pump with Basal-IQ Technology in the US
August 19, 2018 - Innovative platform developed to destroy cancer cells
August 19, 2018 - Lowering pH inside tumor cells can slow down spread of cancer
August 19, 2018 - Biomarker predicts kidney cancer risk years before diagnosis
UCLA researchers reveal reversibility of Friedreich’s ataxia in mouse models

UCLA researchers reveal reversibility of Friedreich’s ataxia in mouse models

image_pdfDownload PDFimage_print

In children and adults with Friedreich’s ataxia, an inherited disease that causes damage to the nervous system, a loss of coordination typically progresses to muscle weakness and can involve vision, diabetes, and other problems over the course of several years. Until now, mimicking those symptoms and progression in mice for research studies has been difficult.

UCLA researchers, after developing a mouse model of Friedreich’s ataxia that shows symptoms similar to patients, have found that many early symptoms of the disease are completely reversible when the genetic defect linked to the ataxia is reversed. The new findings, which still need to be replicated in humans, appear in the journal eLife.

“Remarkably, most of the dysfunction we were seeing in the mice was reversible even after the mice showed substantial neurologic dysfunction,” said Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics, a UCLA professor of Neurology and Psychiatry, and senior author of the new work. “We were very surprised by the extent to which the mice improved since we had assumed that this degree of behavioral dysfunction would be due to cell loss”

Friedreich’s ataxia can begin causing symptoms in childhood or early adulthood. It causes a loss of coordination, or “ataxia,” that makes patients stumble and stagger, among other early symptoms. The disease is known to be caused by a genetic mutation in the gene FXN. The mutation leads to reduced levels of the protein encoded by FXN, called frataxin. While doctors can manage some specific symptoms, there are no current treatments.

“The lack of treatments for Friedreich’s Ataxia has been frustrating for many and has been, in part, due to the lack of good animal models of the disease,” said Geschwind. “There was really a need for a mouse model to help researchers determine the consequences of whole body reduction of frataxin.”

In the new work, Geschwind and colleagues developed a mouse in which the FXN gene can be blocked by a strand of RNA that’s controlled by an antibiotic. Higher levels of the antibiotic lead to more blockage of the gene, and therefore lower levels of frataxin protein. This system allowed the researchers to have tight control over frataxin levels throughout a mouse’s life, letting the mice develop normally for three months before administering antibiotic to turn down frataxin levels.

After 12 weeks with low frataxin levels, the study found, mice have symptoms similar to those seen in humans with the disease, including weight loss, ataxia, impaired walking, hunched backs, and reduced muscular strength. When the researchers stopped giving antibiotics to the diseased mice, letting frataxin levels return to normal, most of the symptoms disappeared.

The study findings suggest that “quite a bit of dysfunction that’s being seen in patients, in the first few years of disease, represents reversible neuronal dysfunction rather than cell death and loss of neurons,” said Geschwind.

The researchers also used the mouse model to study which other genes and proteins are immediately affected by reductions in frataxin, helping point the way toward new drug targets. They hope to continue this line of work, studying the biochemical changes that occur in conjunction with Friedrich’s ataxia. They’re also making this model available for academic and commercial laboratories that are already pursuing drugs that aim to increase frataxin levels in human patients. In these cases, the new mouse model can be used to test the effectiveness of the drugs.

“Going forward, this model provides an important new potential avenue for therapeutic development,” said Geschwind.​

Tagged with:

About author

Related Articles